Half-life determination of the ground state decay of 167Tm and 168Tm.

Precise determination of half-lives of 167Tm and 168Tm are important for their application in nuclear medicine diagnostics, nuclear forensics, and other nuclear data measurements. We produced 167Tm and 168Tm sources using an α-particle beam bombarded 165Ho target and a series purification steps. A series of 173 measurements was performed over a period of 44 days using a high-purity germanium (HPGe) detector to track the count rate change as a function of time by following the 207.8 keV and 531.5 keV γ-lines to determine the radioactive decay half-life of 167Tm. The measurement of half-life of 168Tm ground state has been performed using the same HPGe γ-ray spectrometer to observe γ-lines at 198.3 keV, 816.0 keV, 184.3 keV, 741.4 keV and 914.9 keV. Weighted least-squares fits of exponential decay curves were performed for the dataset of each γ-ray emission, with final determined half-lives of 9.250(15) d and 93.41(12) d for 167Tm and 168Tm, respectively. The uncertainty budgets are presented and discussed in detail. Our result of 167Tm half-life is consistent with the Evaluated Nuclear Structure Data File (ENSDF) recommended half-life of 9.25(2) d. The outcome of 168Tm half-life determination is longer than the ENSDF recommended half-life of 93.1(2) d. Further independent measurements would be ideal to resolve the discrepancy.

ω-transaminase-catalyzed synthesis of (R)-2-(1-aminoethyl)-4-fluorophenol, a chiral intermediate of novel anti-tumor drugs.

The chiral amine (R)-2-(1-aminoethyl)-4-fluorophenol has attracted increasing attentions in recent years in the field of pharmaceuticals because of its important use as a building block in the synthesis of novel anti-tumor drugs targeting tropomyosin receptor kinases. In the present study, a ω-transaminase (ωTA) library consisting of 21 (R)-enantioselective enzymes was constructed and screened for the asymmetric biosynthesis of (R)-2-(1-aminoethyl)-4-fluorophenol from its prochiral ketone. Using (R)-α-methylbenzylamine, D-alanine, or isopropylamine as amino donor, 18 ωTAs were identified with target activity and the enzyme AbTA, which was originally identified from Arthrobacter sp. KNK168, was found to be a potent candidate. The E. coli whole cells expressing AbTA could be used as catalysts. The optimal temperature and pH for the activity were 35-40 °C and pH8.0, respectively. Simple alcohols (such as ethanol, isopropanol, and methanol) and dimethyl sulfoxide were shown to be good cosolvents. High activities were detected when using ethanol and dimethyl sulfoxide at the concentrations of 5-20%. In the scaled-up reaction of 1-liter containing 13 mM ketone substrate, about 50% conversion was achieved in 24 h. 6.4 mM (R)-2-(1-aminoethyl)-4-fluorophenol was generated. After a simple and efficient process of product isolation and purification (with 98.8% recovery), 0.986 g yellowish powder of the product (R)-2-(1-aminoethyl)-4-fluorophenol with high (R)-enantiopurity (up to 100% enantiomeric excess) was obtained. This study established an overall process for the biosynthesis of the high value pharmaceutical chiral amine (R)-2-(1-aminoethyl)-4-fluorophenol by ωTA. Its applicable potential was exemplified by gram-scale production.